Alkoxide sodium

Mixed ethers may be prepared by the interaction of an. alkyl halide and a sodium alkoxide (Williamson s synthesis), for example ... 

Higher alcohols (> C3) react comparatively slowly with sodium because of the slight solubility of the sodium alkoxide in the alcohol a large excess (say, 8 mols) is therefore employed. The mixed ether is distilled off, and the process (formation of alkoxide and its reaction with the alkyl halide) may be repeated several times. The excess of alcohol can be recovered. cj/cloAliphatic alcohols form sodio compounds with difficulty if small pieces... 

Only esters containing two a-hydrogen atoms (ethyl acetate, propionate, n-butyrate, etc.) can be condensed with the aid of sodium alkoxides. For esters with one a-hydrogen atom, such as ethyl tsobutyrate, the more powerful base sodium triphenylmethide PhaC Na leads to condensation with the formation of ethyl a-tsobutyrylisobutyrate ... 

The acetoacetic ester condensation (involving the acylation of an ester by an ester) is a special case of a more general reaction term the Claisen condensation. The latter is the condensation between a carboxylic ester and an ester (or ketone or nitrile) containing an a-hydrogen atom in the presence of a base (sodium, sodium alkoxide, sodamide, sodium triphenylmethide, etc.). If R—H is the compound containing the a- or active hydrogen atom, the Claisen condensation may be written ... 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

When butyrolactone and alcohols are heated for long times and at high temperatures in the presence of acidic catalysts, 4-alkoxybutytic esters are formed. With sodium alkoxides, sodium 4-alkoxybutyrates are formed (150). 

The g-methylene group of butyrolactone condenses easily with a number of different types of carbonyl compounds eg, sodium alkoxides cataly2e self-condensation to a-dibutyrolactone (155), ben2aldehyde gives a-ben2yhdenebutyrolactone (156), and ethyl acetate gives a-acetobutyrolactone (157). 

RandomiZation/Interesterification. Transesterification occurs when a carboxyUc acid (acidolysis) or alcohol (alcoholysis) reacts with an ester to produce a different ester (20). Ester—ester interchange is also a form of transesterification. If completely unsaturated triglyceride oil (UUU) reacts with a totally saturated fat (SSS) in the presence of an active catalyst such as sodium, potassium, or sodium alkoxide, triglycerides of intermediate composition may be formed. 

Alkyl hahdes in the presence of silver oxide react with alkyl malates to yield alkoxy derivatives of succinic acid, eg, 2-ethoxysuccinic acid, H00CCH2CH(0C2H )C00H (12,13). A synthetic approach to produce ethers of malic acid is the reaction of malic esters and sodium alkoxides which affords 2-alkoxysuccinic esters (14). 

Other Rea.ctions, The photolysis of ketenes results in carbenes. The polymeriza tion of ketenes has been reviewed (49). It can lead to polyesters and polyketones (50). The polymerization of higher ketenes results in polyacetals depending on catalysts and conditions. Catalysts such as sodium alkoxides (polyesters), aluminum tribromide (polyketones), and tertiary amines (polyacetals) are used. Polymers from R2C—C—O may be represented as foUows. 

Inefficiencies ia the reaction with POCl leads to alternative production of trialkyl phosphates by employing the sodium alkoxide rather than the alkyl alcohol itself Dialkyl aryl phosphates are produced ia two steps. The low molecular weight alcohol iavolved (eg, butyl) first reacts with excess POCl. The neutral phosphate ester is then completed by the iatermediate chloridate reacting with excess sodium arylate ia water. 

Ammonia and alcohol may be used instead of sodium alkoxides to manufacture alkoxides of titanium and other metals such as tirconium, hafnium, germanium, niobium, tantalum, aluminum, and tin. 

Treatment of cyanopyiidines such as (25) with a Giignaid reagent yields a ketone (32). A carboxyhc ester is obtained by reaction of the nitrile (25) with sodium alkoxide, followed by hydrolysis (33). 

Succinic esters condense with aldehydes and ketones in the presence of bases, eg, sodium alkoxide or piperidine, to form monoesters of alkybdenesuccinic acids, eg, condensation of diethyl succinate with acetone yields ethyl 2-isopropyhdenesuccinate (eq. 3). This reaction, known as Stobbe condensation, is specific for succinic esters and substituted succinic esters (98,99). 

Mixed esteis aie synthesized by the leaction of one alkyl chloiosulfate with a diffeient sodium alkoxide oi a diffeient dialkyl sulfite as follows (92) ... 

Nucleophilic Reactions. Useful nucleophilic substitutions of halothiophenes are readily achieved in copper-mediated reactions. Of particular note is the ready conversion of 3-bromoderivatives to the corresponding 3-chloroderivatives with copper(I)chloride in hot /V, /V- dim ethyl form am i de (26). High yields of alkoxythiophenes are obtained from bromo- and iodothiophenes on reaction with sodium alkoxide in the appropriate alcohol, and catalyzed by copper(II) oxide, a trace of potassium iodide, and in more recent years a phase-transfer catalyst (27). 

Addition of lithium or sodium alkoxide to TYZOR TPT gives a double alkoxide derivative, MTi2(OR), the stmcture of which has been proposed (157) as follows, where M = Na or Li. 

Another better studied system is the Alfin (alkoxide—olefin) catalyst, which is composed of a sodium salt, sodium alkoxide, and aHylsodium (222). Similarly, there are many different modifications of the system to produce polymers with different 1,2- to 1,4-addition ratios as well as other properties (223). 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

The catalyst of choice for this reaction is the corresponding sodium alkoxide. 

Reaction of Enolate Anions. In the presence of certain bases, eg, sodium alkoxide, an ester having a hydrogen on the a-carbon atom undergoes a wide variety of characteristic enolate reactions. Mechanistically, the base removes a proton from the a-carbon, giving an enolate that then can react with an electrophile. Depending on the final product, the base may be consumed stoichiometricaHy or may function as a catalyst. Eor example, the sodium alkoxide used in the Claisen condensation is a catalyst ... 

When 6-amino-3-chloropyridazine 1-oxide is diazotized in 50% sulfuric acid, 6-hydroxy-3-pyridazinediazonium anhydro salt is formed. An azido group at either position in pyridazine A-oxides can readily be replaced with sodium alkoxides. 

Finally the preformed 2-formyl-3-aminoquinoxaline (448) gave the pyrido[2,3-f ]quin-oxalin-2-one (449) with activated esters/sodium alkoxide (79ZC422). 

A benzyl carbonate was prepared in 83% yield from the sodium alkoxide of glycerol and benzyl chloroformate (20°, 24 h). It is cleaved by hydrogenolysis (H2/ Pd-C, EtOH, 20°, 2 h, 2 atm, 76% yield) and electrolytic reduction (-2.7 V, R4N X, DMF, 70% yield). A benzyl carbonate was used to protect the hy-droxyl group in lactic acid during a peptide synthesis. 

Sulfuric acid is also a very satisfactory catalyst aluminum alkoxides also are useful, especially when the alcohols would be adversely affected by strong acids. Sodium alkoxides produce undesirable side reactions and give lower yields. When alkaline catalysts are employed, an alkaline polymerization inhibitor, such as j j-phenylenediamine or phenyl-d-naphthylamine, should be used instead of hydroquinone. 

The use of potassium hydroxide rather than sodium hydroxide is dietated by solubility characteristics which make purification of the sodium alkoxide difficult. 

Sodium alkoxide Sodium azide Sodium borohydride Tetrabromoethane Tetrachloroethane... 

Reaction of 1,4 dibromohexafluoro 2 butene with sodium alkoxides gives products of allylic rearrangement by an S[,j2 process [/7] (equation 16)... 

The reactions of (NSC1)3 with sodium alkoxides to give (NSOR)... 

AsXs and SbXs react with alcohols (especially in the presence of bases) and with sodium alkoxide to give arsenite and antimonite esters, M(0R)3 (cf. phosphorus, (p. 515) ... 

The mechanism of this variant of the Gabriel-Colman reaction has been investigated. Treatment of saccharine derivatives 45-48 with 1-2 equivalents of sodium alkoxide at room temperature provides esters 49-52 in good yields treatment of 45-48 with sodium alkoxide at reflux provides the expected benzothiazines 53-56. Increased concentration leads to higher yields. 

Transetherifications of alkoxy and aryloxy heterocycles with alkoxides have been observed (Sections III,B and IV, B), In 2,4-dialkoxyquinazoline, only the 4-alkoxy group exchanges. When 3-chloro-6-methox3rpyridazine was treated with sodium alkoxides. 

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